The overall objectives of the project are the total synthesis of prostaglandin endoperoxide, the pivotal intermediate in prostaglandin and thromboxane biosynthesis, and a study of its bioconversion into prostaglandins. Since the endoperoxide nucleus is an unusually strained secondary dialkyl peroxide, it is expected to be exceedingly base sensitive. Therefore, all proposed approaches to the synthesis involve neutral or mildly acidic reaction conditions. Approaches presently under investigation include intramolecular peroxymercuration of olefins and cyclopropanes, trapping of singlet oxygen-cyclopentadiene cycloadducts, and alkylation of alkyl hydroperoxides and hydrogen peroxide with diazo compounds and alkyl trifluoromethane sulfonates. The purity of prostaglandin endoperoxide preparations obtained by bioconversion has been questioned. Therefore, understanding of the chemistry involved in the conversion of endoperoxide into prostaglandins, thromboxanes, or malonaldehyde and hepadecapolyenoic acids, especially regarding the role of catalysts, cannot be obtained by studies of these biochemical preparations. This understanding will be obtained by studies on the rearrangement of synthetic endoperoxides and simple models which are being synthesized in this project. Since prostaglandins, endoperoxides, and thromboxanes all exhibit numerous and different biological activities, it is important to know the details of the processes which interconvert these natural products. The total synthesis toward which these studies are directed will provide endoperoxide in sufficient quantities and of known purity for research and eventual medicinal applications. BIBLIOGRAPHIC REFERENCE: "Zero Bridge Cleavage and Neighboring Hydroxyl Group Effect in the Oxymercuration of Bicyclo(3.1.0)hexanes", R.G. Salomon and R.D. Gleim, J. Org. Chem., 41, in press (1976).